Bacterial drug resistance and HIV continue to threaten control of tuberculosis, a communicable disease responsible for well over one million deaths annually [41]. However, after decades of stasis, recent investment in tuberculosis basic science research has resulted in the emergence of new drugs and diagnostics. Critical challenges and opportunities lie in translating recent research advances and new tools into tuberculosis public health practice; historically the tuberculosis field has been vexingly slow in this regard. Pragmatic clinical trials are a promising mechanism to address this challenge [3]. Specifically, pragmatic trials will help to understand the effectiveness of new interventions under usual-care conditions, and to disseminate to practitioners and programs experience with those interventions. Pragmatic clinical trials may be particularly well-suited to tuberculosis, in which centralized clinical data collection and outcome reporting are programmatic norms - this is analogous to how electronic medical record systems are facilitating conduct of pragmatic trials in diabetes, cardiovascular disease, and other health fields. While the idea of pragmatic trials in tuberculosis is not entirely new, to date there has been no focused, systematic exploration of the design of tuberculosis pragmatic trials, regulatory facets of tuberculosis pragmatic trials, an strategies for pragmatic trial implementation across a variety of settings and research questions. The career development goal of this K24 proposal is to expand my knowledge of pragmatic trials, to systematically explore facets of the design and implementation of tuberculosis pragmatic trials, and to design and obtain funding for one or more large pragmatic trials in tuberculosis treatment or diagnosis. Our team's patient-oriented tuberculosis research, which will be the context for mentoring under this K24, is focused on explanatory clinical trials of tuberculosis therapeutics and diagnostics - that is, whether new drugs and tests work under ideal conditions. Much of this work is done in the context of research consortia in which I have leadership roles. I serve as a PI of the NIH/NIAID Tuberculosis Clinical Diagnostics Research Consortium (TB-CDRC), and lead phase 2 and phase 3 therapeutics trials within the CDC Tuberculosis Trials Consortium (TBTC). Our work in these consortia has been at the vanguard of implementation of highly quality monitored, strictly implemented clinical studies (including laboratory components) intended to produce results with the highest possible internal validity. A detailed understanding of tuberculosis clinical trials, along with knowledge and experience in tuberculosis public health program work, provides a very strong foundation from which to undertake new research into pragmatic trials aimed at understanding external validity (generalizability) of new tuberculosis interventions. With respect to mentoring, there is unprecedented opportunity arising from the surge in interest among young health professionals in careers in tuberculosis, HIV, and global health. I have a strong track record in mentoring, including having mentored one infectious disease physician through a successful NIH K23 project and on to independent R01 funding. K24 funding will provide protected time for expansion of mentoring activities. This K24 proposal lies at the nexus of the needs and opportunities for translating tuberculosis research into practice and for training the next generation of investigators in patient-oriented research in tuberculosis. The specific aims are: Aim 1: To directly mentor junior investigators in patient-oriented research in tuberculosis. Mentorship will be principally in the context of research consortia in which I have leadership roles (NIH Tuberculosis Clinical Diagnostics Research Consortium and CDC Tuberculosis Trials Consortium). Junior investigators will be mentored as they take on roles within main consortium studies and/or lead smaller add-on projects that leverage ongoing consortium activities. Aim 2: To develop and implement a model for mentoring within clinical research consortia. Initial work will focus on developing and implementing a mentoring program within the Tuberculosis Clinical Diagnostics Research Consortium and Tuberculosis Trials Consortium. A toolkit will be developed, and then used to expand the model to other clinical research consortia, for example the CDC Tuberculosis Epidemiologic Studies Consortium and the NIH AIDS Clinical Trials Consortium. Aim 3: To build my skills and knowledge in the conduct of pragmatic trials in tuberculosis, in order to conduct future pragmatic trials to assess whether and which new tuberculosis treatments and/or diagnostics work in routine practice. This will be accomplished through interaction with experts in the field of pragmatic trials (Prof. Andrew Nunn and Dr. Jeremy Sugarman), coursework undertaken at Johns Hopkins Bloomberg School of Public Health, engagement in the NIH Health Care Systems Research Collaboratory, and interviews with key stakeholders in the tuberculosis field.